Exercise training-induced benefits for Alzheimer's disease are associated with modulation of the BDNF-TrkB signaling complex.

The mechanism(s) by which exercise training induces multiple beneficial effects for Alzheimer's disease (AD) patients are not well-understood. This study aimed to examine the link between the brain-derived neurotrophic factor (BNDF)-tropomyosin receptor kinase B (TrkB) signaling complex and the beneficial effects of exercise training on cognitive impairment and neuropathology due to AD. At 4 months of age, twenty triple transgenic mice of AD (3x-Tg AD) were randomly assigned to either an AD control (n = 10) or AD exercise (n = 10) group. In parallel, twenty wild-type mice were randomly assigned to either a wild-type control (n = 10) or wild-type exercise (n = 10) group. After 20 weeks of treadmill running, the Morris water maze test was performed, and the mice were then sacrificed for biochemical analyses of plasma and brain tissues. The results indicated that 20 weeks of treadmill running upregulated markers of the BDNF-TrkB signaling complex and mitigated AD neuropathology, along with full recovery from AD-like cognitive impairments. Exercise training also decreased inflammatory cytokines, increased anti-inflammatory cytokines, shifted microglia and astrocytes toward anti-inflammatory phenotypes, improved mitochondrial function, reduced markers of myelin damage, and reduced apoptotic neuronal cell death. In summary, our study findings suggest that exercise training-induced recovery of AD-like cognitive impairments and mitigation of AD neuropathologic biomarkers are associated with modulation of the BDNF-TrkB complex and downstream signaling pathways in 3xTg-AD mice.